Drugs may be delivered to patients by a variety of methods including oral, intravenous administration, inhalation of aerosols, a transdermal patch, and subcutaneous implants. The method chosen depends, among other things, upon the desired therapeutic concentration of the drug or pharmaceutical to be achieved in the patient and the duration the concentration must be maintained.
Subcutaneous implants are introduced under a patient's skin and allow a drug or other pharmaceutical material to be subcutaneously introduced or administered to the patient. In general, a drug administered by a subcutaneous implant is slowly released over a long period of time allowing a uniform dose of the drug to be dispensed over many months or years.
The size and shape of an implant are important in determining the rate of delivery of a particular drug from a subcutaneous implant. Practical considerations put constraints on the dimensions of a subcutaneous implant. For example, the length of a typical implant is generally limited to about 1½ to 2 inches long because longer implants are difficult to accurately position, may be more susceptible to breakage, which can affect drug delivery rate, and in general, are more cumbersome and cosmetically apparent. Because of this, it may be necessary to implant a plurality of individual, shorter implants to provide the desired amount of a drug rather than as a single longer implant. However, administering more than one implant can also be time consuming, cumbersome and cost-prohibitive.
The active agent administered using subcutaneous implants, such as, for example, a drug or pharmaceutical material, may be imbedded in cartridges made of biologically inert polymers. In such cases, cartridges are generally cylindrical hollow tubes made by extrusion, injection molding, reaction injection molding, compression molding, or spin-casting depending on the type of polymer used. Such cylindrical hollow tubes may have one or two open ends. For example, U.S. Pat. Nos. 5,266,325, 5,292,515, and 6,361,797, herein incorporated by reference in their entireties, describe methods for spin casting suitable cartridges. Following molding or casting, the active agent may be introduced into the hollow core, or reservoir of the cartridge, usually in the form of a pellet. Additional liquid material that is polymerizable may be introduced into the core opening and cured to seal the cartridge.
Release agents to aid in removal of a cartridge from a mold are well known in the art. Such release agents are generally dip-coated, sprayed or painted onto or into the mold, and allow molded polymerized material, which may otherwise adhere to the mold, to be easily ejected from the mold. However, residual release agents may adhere to molded articles, and, in the case of an implant device that must be clean and sterile, these release agents must either be removed from the surface of the implant device or be made of a material that can be introduced into a patient without inducing a negative reaction.
The problem of leaving residual release agents, discussed above, can, perhaps, be circumvented by combining a release agent with polymerizable material that will ultimately form the cartridge, prior to introducing the polymerizable material to a mold—provided, of course, that the release agent must be safe for introduction into a patient and must not adversely react with the polymer of the molded article, to cause, for example, weakening of the structure of the article. Accordingly, in one aspect of the invention, effective release agents are provided that do not react undesirably with the polymer of the cartridge and can be safely introduced into a patient. Additionally, selected release agents, as described further below, protect the polymer cartridge from adverse effects of sterilization.